BACKGROUND: Mucosal healing has become an important goal of Crohn's disease (CD) treatments. Modulen, enriched with transforming growth factor-beta 2, and budesonide are commonly accepted treatments for mild-moderate CD. However, their effects on the small bowel (SB) mucosa remain underexplored. AIM: To prospectively assess clinical and mucosal responses to Modulen vs budesonide in adults with CD, using SB capsule endoscopy. METHODS: Thirty patients were divided into two groups: Modulen + home-based diet (21 patients) and budesonide (9 patients) for an eight-week intervention followed by four weeks of follow-up. Clinical, laboratory, and endoscopic responses were evaluated. The mucosal changes were assessed through SB capsule endoscopy. RESULTS: Results indicated significant clinical improvement in the Modulen group with reduced CD activity index (P = 0.041) and improved inflammatory bowel disease questionnaire score (P = 0.016). Moreover, Modulen was associated with a significant SB mucosal improvement, evidenced by a decrease in Lewis score (P = 0.027). No significant changes were observed in calprotectin or other laboratory parameters. Conversely, budesonide exhibited more modest clinical effects, but it improved calprotectin, hemoglobin, and C-reactive protein levels (P = 0.051, P = 0.014, and P = 0.038, respectively). The capsule endoscopy did not reveal a significant mucosal response in the budesonide group. CONCLUSION: Both interventions have a role in CD treatment. Yet, their effects differ and may complement each other: Modulen yields clinical and mucosal improvements, while budesonide primarily leads mainly to laboratory improvements.